Renal toxicity and gouty arthritis (saturnine gout) are two of the diverse symptoms of lead poisoning. A study of the effects of lead on the enzymes of purine metabolism was initiated to uncover the etiology of saturnine gout. The study showed that the enzyme (guanase) was exquisitely sensitive to Pb2 ion. The role of guanase is to convert guanine to xanthine. Guanine is very insoluble and lead poisoning may lead to accumulation of guanine precipitates (in vivo). Using the pig as an animal model, a five-fold increase in guanine was observed in extracellular fluid and crystalline concretions which were identified as guanine were observed in the region of the femoral head. Hg2 ion and Ag ion but not Cd2 ion or any other metal that we tested was inhibitory to guanase at low concentrations. This proposal is to extend these studies of the effects of Pb2 ion on purine metabolism to primates, since purine metabolism in primates and humans is somewhat different than in the lower mammals. Extracellular fluid from lead-poisoned patients will also be examined. These studies will entail the induction of saturnine gout in marmosets and administration of (14C) guanine to poisoned and normal animals to determine in which organs guanine accumulates. The effects of Pb2 ion and Hg2 ion on guanase are synergistic, and we will determine if this synergistic effect is elicited in vivo. Finally, a tissue distribution guanase has been carried out and the most striking finding was the presence of high guanase activity in the brain of each species tested. Therefore, the possible elicitation of CNS manifestation by Pb2 ion and Hg2 ion via elevation of nervous tissue guanine will be investigated. Lead and mercury are volatile components of coal and lead is an atmospheric contaminant due to its continued use in gasoline. Mercury is a water contaminant. Therefore, this study would give an indication of the extent to which these pollutants give rise to CNS, renal and metabolic problems related to the accumulations of the highly insoluble metabolite guanine.